本文采用的英格恩产品: Entranster-D4000, Entranter-R4000
Lactate Induces Production of the tRNAHis Half to Promote B-lymphoblastic Cell Proliferation
Affiliations
- 1 Department of Dermatology, Renji Hospital, School of Medicine & ShengYushou Center of Cell Biology and Immunology, Joint International Research Laboratory of Metabolic & Development Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, P.R. China; MOE & NHC & CAMS Key Laboratory of Medical Molecular Virology, Department of Medical Microbiology and Parasitology, School of Basic Medical Science, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China; Central Laboratory, Shanghai Dermatology Hospital, Shanghai 200443, P.R. China.
- 2 MOE & NHC & CAMS Key Laboratory of Medical Molecular Virology, Department of Medical Microbiology and Parasitology, School of Basic Medical Science, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China.
- 3 Department of Dermatology, Renji Hospital, School of Medicine & ShengYushou Center of Cell Biology and Immunology, Joint International Research Laboratory of Metabolic & Development Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, P.R. China.
- 4 Division of Hematology, Shanghai First People’s Hospital, Shanghai Jiao Tong University, Shanghai 200080, P.R. China.
- 5 Central Laboratory, Shanghai Dermatology Hospital, Shanghai 200443, P.R. China. Electronic address: tanfeitrue@126.com.
- 6 Department of Dermatology, Renji Hospital, School of Medicine & ShengYushou Center of Cell Biology and Immunology, Joint International Research Laboratory of Metabolic & Development Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, P.R. China. Electronic address: fangwei@sjtu.edu.cn.
- 7 MOE & NHC & CAMS Key Laboratory of Medical Molecular Virology, Department of Medical Microbiology and Parasitology, School of Basic Medical Science, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China; Expert Workstation, Baoji Central Hospital, Baoji 721008, P.R. China. Electronic address: qiliang@fudan.edu.cn.
- PMID: 32966775
- PMCID: PMC7647672
- DOI: 10.1016/j.ymthe.2020.09.010
Abstract
High plasma lactate is emerging as a critical regulator in development and progression of many human malignancies. Small RNAs derived from cleavage of mature tRNAs have been implicated in many cellular stresses, but the detailed mechanisms that respond to lactic acid (LA; acidic lactate) are not well defined. Here, using an Epstein-Barr virus (EBV)-immortalized B lymphoblastic cell line (LCL) as a model, we report that LA induces cleavage of mature tRNA at the anticodon loop, particularly production of three 5′-tRNA halves (5′-HisGUG, 5′-ValAAC, and 5′-GlyGCC), along with increased expression of RNA polymerase III and angiogenin (ANG). Of these, only the 5′-HisGUG half binds to the chromatin regulator argonaute-2 (AGO2) instead of the AGO1 protein for stability. Notably, the levels of ANG and 5′-HisGUG half expression in peripheral blood mononuclear cells from B cell lymphoma patients are tightly correlated with lactate dehydrogenase (LDH; a lactate indicator) in plasma. Silencing production of the 5′-HisGUG half by small interfering RNA or inhibition of ANG significantly reduces colony formation and growth of LA-induced tumor cells in vitro and in vivo using a murine xenograft model. Overall, our findings identify a novel molecular therapeutic target for the diagnosis and treatment of B cell lymphoma.
Keywords: B-lymphoma; cell proliferation; lactate; tRNA half.
